Clinical Outcomes After Ustekinumab Biosimilar Switching in Crohn’s Disease: The USBIOS–Italian Group for the Study of Inflammatory Bowel Disease Study

Background & aims: Controlled real-world evidence on nonmedical switching from reference ustekinumab to biosimilars in Crohn's disease (CD) is limited. We compared 6-month outcomes after switching vs continued reference treatment. Methods: In this prospective observational cohort at 18 Italian centers, adults with CD in clinical remission (Harvey-Bradshaw Index <5) and steroid-free for ≥8 months of reference ustekinumab, underwent a procurement-driven switch to 1 of 3 approved biosimilars or continued reference treatment. The expanded clinical success end point required clinical remission without systemic corticosteroids, anti-interleukin12 or 23 discontinuation, inflammatory bowel disease-related hospitalization, or intestinal surgery. The protocol-specified noninferiority margin was -15%. Results: Among 462 patients, 337 switched and 125 continued reference ustekinumab; only 4 (0.9%) received every-4-week dosing. Expanded clinical success occurred in 306 of 332 switched patients (92.2%) and 114 of 123 controls (92.7%; risk difference, -0.5%, 95% confidence interval, -5.9 to 4.9), meeting the noninferiority criterion. Results were consistent for the protocol-defined 3-component composite and after propensity-score weighting. Biosimilar persistence was 93.7%; switch-back occurred in 1.2%. Two adverse events were reported after switching. Conclusions: In clinically stable CD, the observed 6-month effectiveness and safety after procurement-driven ustekinumab biosimilar switching were similar to continued reference treatment. Longer-term studies, particularly in patients receiving every-4-week dosing, are needed.